Angelica Acutiloba Research Articles

Germination characteristics of Angelica gigas and Angelica acutiloba as affected by cold stratification and hot water treatment before sowing

Germination characteristics of <i>Angelica gigas</i> and <i>Angelica acutiloba</i> as affected by cold stratification and hot water treatment before sowing

Selective induction of furanocoumarins in Angelica acutiloba roots by signaling molecule, ethylene and their monoamine oxidase inhibition

The level of bioactive metabolites is the most critical factor to become a functional food material. This study offered the practical method to enhance furanocoumarins (FCs) content in Angelica acutiloba which is an herbal vegetable and functional food ingredient. FCs content in root part was significantly increased by the treatment of the signaling molecule, ethylene. Newly increased FC derivatives were annotated as xanthotoxin (XAT), psoralen (PSR), isopimpinellin (IPP), and bergapten (BGT). The contents of FCs continued to increase until they reached the level where XAT (54-fold, 64.9 μg/g → 3499 μg/g), PSR (7-fold, 31.9 μg/g → 214 μg/g), IPP (23-fold, 16.2 μg/g → 375 μg/g), and BGT (51-fold, 29.5 μg/g → 1512 μg/g). Hereby, the content of FC derivatives increased selectively, and other metabolites were not affected by ethylene. The metabolite changes were systematically investigated using UPLC-ESI-Q-TOF/MS analysis to obtain a clear difference in the PLS-DA score, S-plot, and heatmap to explain the gradual fluctuation in the metabolite levels over the treatment time (96 h). Additionally, FCs enriched roots showed a distinctive inhibitory activity against monoamine oxidase (MAO-A and B) compared to control roots because of the increased FCs content. A. acutiloba with greatly enhanced FCs content is applicable as functional food material for new purposes.

Ligustilide, A Novel Senolytic Compound Isolated from the Roots of Angelica Acutiloba.

Senescent cells accumulate with age and contribute to age-related diseases and organ dysfunctions. Early evidence suggests that removal of senescent cells using senolytic drugs improves the aging phenotype in mice and may improve the health of individuals with chronic diseases. Signs of skin aging, including wrinkles, and sagging, occur largely due to the accumulation of senescent fibroblasts within the dermis; However, there is currently no skin treatment that eliminates senescent cells. In this study, human fibroblasts subjected to replicative aging and ionizing radiation exposure are used to screen plant extracts for potential senescent cell-destructive and/or senescent cell-forming activities. Angelica acutiloba-a traditional Chinese herbal medicine-selectively kills senescent cells without affecting the proliferating cells. Among the major components of this herb, ligustilide shows promising senescent cell-destructive properties, and selectively eliminates senescent cells by inducing an apoptosis. Moreover, ligustilide markedly inhibits senescence-associated secretory phenotypes. Administration of ligustilide to mouse skin eliminates senescent cells and increases dermal collagen density and subcutaneous adipose tissue content; it selectively promotes death of senescent cells without affecting non-senescent cells. These results provide evidence that a natural compound-ligustilide-may exhibit therapeutic effects on the skin aging phenotype by specifically inducing apoptosis in senescent cells.

Angelica acutiloba Kitagawa flower induces A549 cell pyroptosis via the NF-κB/NLRP3 pathway for anti-lung cancer effects

Angelica acutiloba Kitagawa, a traditional medicinal herb of the Umbelliferae family, has been demonstrated to have anticancer activity. In this study, we investigated the anti-lung cancer effects of two compounds extracted from A. acutiloba flowers: kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside (KAE) and platanoside (PLA). MTT, cell colony formation, and cell migration (scratch) assays revealed that both KAE (100 μM) and PLA (50 μM and 100 μM) inhibited the viability, proliferation, and migration of A549 cells. Dichlorodihydrofluorescein diacetate assays showed that KAE and PLA also induced the generation of reactive oxygen species in A549 cells. Morphologically, A549 cells swelled and grew larger under treatment with KAE and PLA, with the most significant changes at 100 μM PLA. Fluorescence staining and measurement of lactate dehydrogenase release showed that the cells underwent pyroptosis with concomitant upregulation of interleukin (IL)-1β and IL-18. Furthermore, both KAE and PLA induced upregulation of NF-κB, PARP, NLRP3, ASC, cleaved-caspase-1, and GSDMD expression in A549 cells. Subsequent investigations unveiled that these compounds interact with NLRP3, augment NLRP3’s binding affinity with ASC, and stimulate the assembly of the inflammasome, thereby inducing pyroptosis. In conclusion, KAE and PLA, two active components of A. acutiloba flower extract, had significant anti-lung cancer activities exerted through regulation of proteins related to the NLRP3 inflammasome pathway.

Didymella acutilobae sp. nov. Causing Leaf Spot and Stem Rot in Angelica acutiloba

During disease surveys of Angelica acutiloba plants in Korea, leaf spot symptoms were observed in a field in Andong in July 2019, and stem rot symptoms in vinyl greenhouses in Yangpyeong in April 2020. Incidence of leaf spot and stem rot of the plants ranged from 10 to 20% and 5 to 30%, respectively. Morphological and cultural characteristics of fungal isolates from the leaf spot and stem rot symptoms fitted into those of the genus Phoma. Molecular phylogenetic analyses of two single-spore isolates from the symptoms using concatenated sequences of LSU, ITS, TUB2, and RPB2 genes authenticated an independent cluster from other Didymella (anamorph: Phoma) species. Moreover, the isolates showed different morphological and cultural characteristics in comparison to closely related Didymella species. These discoveries confirmed the novelty of the isolates. Pathogenicity of the novel Didymella species isolates was substantiated on leaves and stems of A. acutiloba through artificial inoculation. Thus, this study reveals that Didymella acutilobae sp. nov. causes leaf spot and stem rot in Angelica acutiloba.

Network medicine framework identified drug-repurposing opportunities of pharmaco-active compounds of Angelica acutiloba (Siebold & Zucc.) Kitag. for skin aging.

Increasing incidence of skin aging has highlighted the importance of identifying effective drugs with repurposed opportunities for skin aging. We aimed to identify pharmaco-active compounds with drug-repurposing opportunities for skin aging from Angelica acutiloba (Siebold & Zucc.) Kitag. (AAK). The proximity of network medicine framework (NMF) firstly identified 8 key AAK compounds with repurposed opportunities for skin aging, which may exert by regulating 29 differentially expressed genes (DGEs) of skin aging, including 13 up-regulated targets and 16 down-regulated targets. Connectivity MAP (cMAP) analysis revealed 8 key compounds were involved in regulating the process of cell proliferation and apoptosis, mitochondrial energy metabolism and oxidative stress of skin aging. Molecular docking analysis showed that 8 key compounds had a high docked ability with AR, BCHE, HPGD and PI3, which were identified as specific biomarker for the diagnosis of skin aging. Finally, the mechanisms of these key compounds were predicted to be involved in inhibiting autophagy pathway and activating Phospholipase D signaling pathway. In conclusion, this study firstly elucidated the drug-repurposing opportunities of AAK compounds for skin aging, providing a theoretical reference for identifying repurposing drugs from Chinese medicine and new insights for our future research.

Classification of Angelica species found in various foods using an LC-QTOF/MS-based metabolomics approach

In Korea, Angelica gigas is commonly known as Danggui. However, two other species on the market, Angelica acutiloba and Angelica sinensis, are also commonly called Danggui. Since the three Angelica species have different biologically active components, thus, different pharmacological activities, clear discrimination between them is needed to prevent their misuse. A. gigas is used not only as a cut or powdered product but also in processed foods, where it is mixed with other ingredients. To discriminate between the three Angelica species, reference samples were analysed as non-targeted using liquid chromatography-quadrupole time of flight/mass spectrometry (LC-QTOF/MS) and a metabolomics approach in which a discrimination model was established by partial least squares-discriminant analysis (PLS-DA). Then, the Angelica species in the processed foods were identified. First, 32 peaks were selected as marker compounds and a discrimination model was created using PLS-DA, and its validation was confirmed. Classification of the Angelica species was undertaken using the YPredPS value, and it was confirmed that all 21 foods examined contained the appropriate Angelica species indicated on the product packaging. Likewise, it was confirmed that all three Angelica species were accurately classified in the samples to which they were added.

Chemical composition and anti-aging effects of standardized herbal chicken essence on D-galactose- induced senescent mice.

This study aimed to examine the chemical and anti-aging properties of chicken essence (CE) prepared with Sesamum indicum, Angelica acutiloba, and Zingiber officinale (HCE). HCE was analyzed for nutritional and phytochemical composition, and its anti-aging effects were investigated on the D-galactose (Gal)-induced aging mice. Results showed that HCE possessed significantly higher calories and contents of valine and total phenols than CE; it also contained significant amounts of ferulic acid, sesamin, and sesamolin. HCE significantly decreased MDA and NO levels in serum and liver and increased liver GSH levels in the D-Gal-induced mice. HCE greatly enhanced SOD and CAT activities in serum and liver, and liver GPx activity, as well as upregulating SIRT1 expression and downregulating TNF-α, IL-1β, IL-6, iNOS, Cox-2, and MCP-1 expression in liver tissues. This study demonstrates that HCE was effective in suppressing the aging process through enhancing antioxidant and anti-inflammatory activities and modulating the aging-related gene expression.

Discrimination of three Angelica herbs using LC-QTOF/MS combined with multivariate analysis

Angelica gigas, a popular medicinal herb in Korea, is locally called Danggui; this name is similarly used for Angelica acutiloba and Angelica sinensis, which are also sold in the retail market. These three herbs have differing therapeutic effects and should be used according to their prescribed purposes. In some retail markets, though, all three herbs are known by the same common name rather than a scientific name and can therefore be confused with each other. In particular, in the case of powdered products, intentional or unintentional wrong sales activity by the seller may occur. In this study, non-targeted analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry to discriminate between the three Angelica herbs, and marker compounds were identified by principal component analysis. Principal component analysis was applied to the whole dataset with the variables being sample name, peak name (m/z with retention time), and ion intensity extracted in advance by peak finding, alignment, and filtering. All three herbs were visually and clearly differentiated in the score plot, and the marker compounds that contributed to their discrimination were found in the loading plot through principal component variable grouping (PCVG). Among the marker compounds, coumarins contributed to the classification of A. gigas, and phthalides contributed to the classification of A. sinensis. The three Angelica herbs were well discriminated from each other. Within the three Angelica species investigated, marker compounds can determine the species of even powdered or extracted samples that cannot be visually identified.

ASSESSMENT OF THE GROWTH AND YIELD OF ANGELICA ACUTILOBA KIT. AND SALVIA MILTIORRHIZA BUNGE GROWN IN HONG THAI COMMUNE, NA HANG DISTRICT, TUYEN QUANG PROVINCE

Angelica acutiloba Kitagawa was immigrated to Vietnam in 1990 and Salvia mitiorrhiza Bunge was immigrated to Vietnam in the 1960s from China. Currently, both herbs are grown and developed in various places. They are precious medicinal plants, are important medicinal plants in many traditional medicines. Research results show that tuber diameter is 0.79cm, tuber length is 27.8cm, yield is 68.8g/plant or Salvia mitiorrhiza Bunge; reached 1.80cm in tuber diameter, 19.0cm in tuber length and yield is 16.0g/ plant for the Angelica acutiloba Kitagawa. The main diseases on Salvia mitiorrhiza Bunge are root rot in an extremely common level; for Angelica acutiloba Kitagawa plants, root rot did not appear, but pests mainly included small snails and leaf folders, with a low degree of prevalence. In general, the growth and development ability of these two species are completely suitable with the soil and climate conditions in Na Hang district as well as other localities with similar conditions.

Establishment of bioreactor cultures for the production of chlorogenic acid and ferulic acid from adventitious roots by optimization of culture conditions in Angelica acutiloba (Siebold &amp; Zucc.) Kitag

Establishment of bioreactor cultures for the production of chlorogenic acid and ferulic acid from adventitious roots by optimization of culture conditions in Angelica acutiloba (Siebold &amp; Zucc.) Kitag

Angelica acutiloba Exerts Antihypertensive Effect and Improves Insulin Resistance in Spontaneously Hypertensive Rats Fed with a High-Fat Diet

Introduction: Angelica acutiloba is one of the crude drugs used in Chinese herbal medicine, and its intake is expected to improve metabolic syndrome-associated disorders. Here, we examined the effects of A. acutiloba extract (AAE) on hypertension and insulin resistance induced by the treatment of high-fat diet (HFD) to spontaneously hypertensive rats (SHRs). Then, we investigated the mechanisms associated with the effects of AAE. Methods: AAE was administered to HFD-fed SHRs. Systolic blood pressure (SBP), sympathetic nerve activity, hypothalamic angiotensin-converting enzyme (ACE) activity, blood glucose level, plasma insulin concentration, visceral fat mass, and gene expression of tumor necrosis factor-alpha (TNF-α) in the visceral fat were evaluated. Results: AAE reduced the increases in SBP and hypothalamic ACE activity observed in the HFD-fed SHRs, whereas the suppressive effect on sympathetic nerve activity was slight. Environmental stress-induced pressure and sympathetic overactivity were suppressed by the treatment of AAE. It also decreased the increase in the blood glucose level, plasma insulin concentration, homeostasis model assessment for the insulin resistance, and TNF-α gene expression in the visceral fat, but not the increase in the visceral fat mass. Conclusion: AAE has an antihypertensive effect, suppresses stress-induced hypertension, and improves insulin resistance in HFD-fed SHRs. The suppression of brain ACE activity, sympathetic nerve activity, and inflammation are partly involved in the effects of AAE.

Isolation and identification of two flavonoid compounds from acclimatized Angelica acutiloba kitagawa growing in Vietnam

Isolation and identification of two flavonoid compounds from acclimatized Angelica acutiloba kitagawa growing in Vietnam

Efficient fertilization in the cultivation of Angelica acutiloba (Siebold & Zucc.) Kitag. in Hokkaido: Effect of amount of supplied nitrogen on growth, yield, and quality of A. acutiloba.

Angelica acutiloba (Siebold & Zucc.) Kitag., the source plant of the crude drug Angelicae acutilobae radix, is traditionally cultivated in western regions of Japan. Since A. acutiloba is now also grown in Hokkaido, the northernmost prefecture of the country, the cultivation method, especially the quantity of fertilizer, needs to be adapted because of the cooler climate and shorter growing period. In this study, we compared plant growth and harvest yield of A. acutiloba cultivated with different amounts of nitrogen (N) fertilizer. When plants were fertilized with 24kgN/10 a, the aerial part was lush, and the diameter at the top of the root was about 1.3 times thicker than that in plants treated with 12kgN/10 a. On the other hand, the weight of the harvested root grown with 24kgN/10 a was slightly, although not significantly, less than that in plants grown with 12kgN/10 a. In addition, we found that the content of (Z)-ligustilide, a major essential oil contained in A. acutiloba root, is affected by nitrogen application. Interestingly, it increased with increasing amounts of supplied nitrogen. However, the importance of Angelicae acutilobae radix as the crude drug is not limited to its (Z)-ligustilide content, and there are also other crucial quality features, such as having thick lateral roots, which were generated in this study with a moderate nitrogen application. We conclude that about 12kgN/10 a is the optimal amount of nitrogen for healthy growth of A. acutiloba in Hokkaido.

First Report of Tomato Spotted Wilt Virus in Angelica acutiloba

In June 2019, Angelica acutiloba plants showing virus-like symptoms such as chlorotic local lesion and mosaic on the leaves were found in a greenhouse in Nonsan, South Korea. To identify the causal virus, we collected 6 symptomatic A. acutiloba leaf samples and performed reverse transcription polymerase chain reaction (RT-PCR) analysis using specific detection primers for three reported viruses including tomato spotted wilt virus (TSWV). RT-PCR results showed that five symptomatic samples were positive for TSWV. Mechanical sap inoculation of one of the collected TSWV isolate (TSWV-NS-AG28) induced yellowing, chlorosis and mosaic symptoms in A. acutiloba and necrotic local lesions and mosaic in Solanaceae species. Phylogenetic analysis based on the complete genome sequences showed that TSWV-NS-AG28 had a maximum nucleotide identity with TSWV-NS-BB20 isolated from butterbur in Nonsan, South Korea. To our knowledge, this is the first report of TSWV infection in A. acutiloba.

Studies on cultivation of Angelica acutiloba using paper pot (Part 2): effect of difference in taproot base diameter of seedlings on growth after planting and quality of toki produced from paper pot seedlings.

By using Angelica acutiloba seedlings produced by short-period raising in paper pot (PP), we investigated the effect of taproot base diameter on the growth after planting and evaluated the quality of toki (, Angelicae Acutilobae Radix) produced from PP-grown seedlings (PT). In this study, PP-grown seedlings of seven classes which are sorted difference taproot base diameter (P1-P7) were transplanted. As a result, the survival rates were not less than 90% for P6 (taproot base diameter: 10.0-12.7cm) and P7 (taproot base diameter: 12.8-17.3cm), and the bolting rates were 20.5% and 24.1% for P6 and P7, respectively. The traditionally grown seedling (TS) showed the highest available harvest rate of 82.3%, followed by P6 (71.8%) and P7 (69.0%). P7 showed the highest fresh weight and dry weight per 1a (100 m2), followed by P6 and TS. However, PP-grown seedlings are prone to bolting, and it is expected the yield can be increased by preventing bolting. In addition, PT satisfied the regulations of JP17 in terms of, for example, dilute ethanol-soluble extract content, total ash content, and acid-insoluble ash content. It was also found that PT has a higher proportion of lateral roots with respect to the total weight than toki produced from traditionally grown seedlings (TT). The total (Z)-ligustilide contents were 0.07% in PT and 0.12% in TT. It was revealed that it is possible to produce toki that satisfies JP17 regulations; moreover, the period required for toki production was shortened by 6months with PP-grown seedlings.

Analysis of Plant Type and Color Preference and Psychological Assessment for Gardening Activities of Firefighters

Background and objective: This study investigated plant type and color preference and conducted a psychological assessment for gardening activities of fire-fighters in a high-risk occupational group.Methods: A survey was conducted on 117 firefighters aged 39.01±9.17 in Sunchang in March 2020 to examine their preferences in plant type and color and conduct a psychological assessment of firefighters on gardening activities.Results: For plant experience and awareness, plant-related event showed the highest score, followed by plant preference tendency and plant growing experience. The level of plant gardening activities was higher among older age and higher job position. As a result of examining the quality of life according to the demographic characteristic with WHOQOL-BREF (World Health Organization Quality of Life Assessment Instrument), it was found that the quality of life was higher among the 20s–30s than 50s, firefighter position than fire lieutenant or higher, those with higher average monthly income, and the singles group than married (p < .05). The administration group showed lower scores than the fire suppression group working in the field, showing statistical significance. Most firefighters showed high preference for herbal plants among the 12 types of flowering plants, in the order of Rosmarinus officinalis > Lavandula spp. > Mentha piperita, Calendula officinalis. Pelargonium spp. was preferred the least out of the flowering plants, Lycopersicon esculentum was preferred the most out of 12 types of vegetable plants, while Angelica acutiloba was preferred the least statistical significance. For the preference of plant colors, yellow was the most preferred color, followed by white, blue, orange, red, and green, showing statistical significance. For the psychological survey responses of emotion words toward 6 plants colors, it was found that ‘bright’ was the emotion felt most strongly by the white, yellow, and orange groups, ‘calm’ and ‘comfortable’ by the green and blue groups, and ‘fancy’ by the red group.Conclusion: The effect of agro-healing programs can be increased by using mostly yellow plants when creating indoor healing gardens at the workplaces of fire officials in a high-risk occupational group, and using herbal plants and Lycopersicon esculentum in the gardens for agro-healing activities.Key words: fancy, fire lieutenant, world health organization quality of life assessment instrument (WHOQOL-BREF)

Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways.

Inflammatory bowel disease (IBD) is a chronic idiopathic disorder causing inflammation in the gastro-intestinal tract, which is lack of effective drug targets and medications. To identify novel therapeutic agents against consistent targets, we exploited a systems pharmacology-driven framework that incorporates drug-target networks of natural product and IBD disease genes. Our in silico approach found that Ligustilide (LIG), one of the major active components of Angelica acutiloba and Cnidium Officinale, potently attenuated IBD. The following in vivo and in vitro results demonstrated that LIG prevented experimental mice colitis induced by dextran sulfate sodium (DSS) via suppressing inflammatory cell infiltration, the activity of MPO and iNOS, and the expression and production of IL-1β, IL-6, and TNF-α. Subsequently, the network analysis helped to validate that LIG alleviated colitis by inhibiting NF-κB and MAPK/AP-1 pathway through activating PPARγ, which were further confirmed in RAW 264.7 cells and bone marrow-derived macrophages in vitro. In summary, this study reveals that LIG activated PPARγ to inhibit the activation of NF-κB and AP-1 signaling thus eventually alleviated DSS-induced colitis, which has promising activities and may serve as a candidate for the treatment of IBD.Graphical abstract This study suggested novel computational and experimental pharmacologyapproaches to identify potential IBD therapeutic agents by exploiting polypharmacology of natural products. We demonstrated that LIG could attenuate inflammation in IBD by inhibiting NF-κB and AP-1 pathways via PPARγ activation to reduce the expression of pro-inflammatory cytokines in macrophages. These findings offer comprehensive pre-clinical evidence that LIG may serve as a promising candidate for IBD therapy in the future. Graphical headlights: 1. Systems pharmacology uncovered Ligustilide attenuates experimental colitis in mice. 2. Network-based analysis predicted the mechanism of Ligustilide against IBD, which was validated by inhibiting PPARγ-mediated inflammation pathways. 3. Ligustilide activated PPARγ to inhibit NF-κB and AP-1 activation thus eventually alleviated DSS-induced colitis.4. Ligustilide has promising activities and may serve as a candidate for the treatment of IBD.

Simultaneous quantitative analysis of five components in Angelica sinensis and Angelica acutiloba acclimatized growing in vietnam by high-performance liquid chromatography with photodiode array detector

Background: Chinese Danggui (Angelica sinensis) and Japanese Danggui (Angelica acutiloba) are evaluated as the same in using and critical of quality control in Vietnamese Pharmacopoeia. In Vietnam, Japanese Danggui were acclimatized and cultivated in several regions in recent years. Despite the huge climatic difference between Vietnam and Japan, Japanese Danggui grows very well in Vietnam. However, there are no studies to assess the overall quality of this medicinal herbs. Aims and Objectives: The aim of this study is to develop a method to identify and assay simultaneously 5 component compounds of these crude herbs: chlorogenic acid, ferulic acid, scopoletin, xanthotoxin and ligustilide by high-performance liquid chromatography with photodiode array detector (HPLC-PDA). Materials and Methods: The procedure was optimized by using column Phenomenex Gemini 5 μm PR C18, 15 x 4,6 mm with the detection wavelength set at 321 nm for detector PDA and mobile phase was composed of (A) ACN and (B) aqueous solution 1% of acid acetic using a gradient elution. Analytes were performed at 30°C with a flow rate of 1.0 mL/min. Results: The developped method were fully validated for linearity, accuracy, recovery and met the validation requirements, proved practical applicability for the quality control of these herbs and related products. Conclusion: The method was successfully applied to the quantification of five markers simultaneously from collected samples.

日本薬局方に見られた向精神・神経薬の変遷（その 22）当帰の成分研究経緯に関する史的考察

日本薬局方に見られた向精神・神経薬の変遷（その 22）当帰の成分研究経緯に関する史的考察